Use of the oncolytic enzyme, L-asparaginase, demonstrated that deprivation of non-essential amino acid could have lethal repercussions on tumor cells. This Section explores alternate means of achieving such deprivations by inhibiting L-asparagine synthetase, L-asparaginyl tRNA synthetase, and stimulating endogenous L-asparaginase activities. Orthrodox drugs and intermediary metabolites are among the agents being examined in a systematic way for such action. In addition, inasmuch as L-glutamine is the ordinary source of the nitrogen of L-asparagine, we are exploring a select number of powerful L-glutamine antagonists for their perturbation of L-asparagine metabolism. The mechanisms of action of new antagonists of L-aspartic and L-glutamic acids with antitumor activity are also being studied preparatory to clinical trials with these agents. Lastly, a small number a new oncolytic enzymes are being subjected to therapeutic and toxicologic testing. BIBLIOGRAPHIC REFERENCES: Kelley, J.M., Adamson, R.H., Cooney, D.A., Jayaram, H.N. and Anandaraj, S.: The Pharmacological Disposition of DL-Alanosine (NSC-143,647) in Mice, Rats, Dogs and Monkeys. Cancer Treat. Rep. (In Press), 1977. Cooney, D.A., Milman, H.A., Cable, R.G., Dion, R.L., Bono, Jr., V.H., Karrer, K. and Friedl, H.P.: Maleimide: Biochemical, Pharmacologic and Toxicologic Studies - Interaction with L-Asparagine Metabolism. Biochem. Pharm. (In Press), 1977.